The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis

Xu, Yin; Ke, Yan; Wang, Bin; Lin, Jianhao

doi:10.1186/s40659-015-0057-0

Cited by 65 publications

(62 citation statements)

References 27 publications

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“…In the context of OA, previous studies demonstrated that chondrocytes upregulate CCL2 expression following inflammatory stimuli 17 27 28. Consistent with this, we found that chondrocytes within OA cartilage tissues abundantly express CCL2 (see online supplementary figure S4E).…”

Section: Resultssupporting

confidence: 89%

“…While it is known that CCL2 is predominantly made by immune cells in humans and mice, other non-immune cell types have also been shown to express CCL2. For instance, previous studies have demonstrated that cultured murine and human chondrocytes upregulate CCL2 expression following inflammatory stimuli 27 28. Furthermore, it is well known that ageing, a major risk factor for OA development, is associated with systemic low-grade inflammation including elevated local and circulating cytokines 43.…”

Section: Discussionmentioning

confidence: 99%

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CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis

et al. 2016

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Objectives While various monocyte chemokine systems are increased in expression in osteoarthritis (OA), the hierarchy of chemokines and chemokine receptors in mediating monocyte/macrophage recruitment to the OA joint remains poorly defined. Here, we investigated the relative contributions of the CCL2/CCR2 versus CCL5/ CCR5 chemokine axes in OA pathogenesis. Methods Ccl2-, Ccr2-, Ccl5- and Ccr5-deficient and control mice were subjected to destabilisation of medial meniscus surgery to induce OA. The pharmacological utility of blocking CCL2/CCR2 signalling in mouse OA was investigated using bindarit, a CCL2 synthesis inhibitor, and RS-504393, a CCR2 antagonist. Levels of monocyte chemoattractants in synovial tissues and fluids from patients with joint injuries without OA and those with established OA were investigated using a combination of microarray analyses, multiplexed cytokine assays and immunostains. Results Mice lacking CCL2 or CCR2, but not CCL5 or CCR5, were protected against OA with a concomitant reduction in local monocyte/macrophage numbers in their joints. In synovial fluids from patients with OA, levels of CCR2 ligands (CCL2, CCL7 and CCL8) but not CCR5 ligands (CCL3, CCL4 and CCL5) were elevated. We found that CCR2+ cells are abundant in human OA synovium and that CCR2+ macrophages line, invade and are associated with the erosion of OA cartilage. Further, blockade of CCL2/CCR2 signalling markedly attenuated macrophage accumulation, synovitis and cartilage damage in mouse OA. Conclusions Our findings demonstrate that monocytes recruited via CCL2/CCR2, rather than by CCL5/CCR5, propagate inflammation and tissue damage in OA. Selective targeting of the CCL2/CCR2 system represents a promising therapeutic approach for OA.

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Section: Resultssupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis

et al. 2016

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“…Furthermore, IL-6 is described to be able to increase MMP expression alone or in synergy with IL-1β and oncostatin M [83][84][85]. In addition, MCP-1 increased MMP-13 expression in chondrocytes [86]. Furthermore, several other proteins that are abundantly present in L-PRF CM, such as RANTES, growth regulated oncogene (GRO) and IL-8 might be responsible for the observed effects in our study [31].…”

Section: Discussionsupporting

confidence: 48%

Therapeutic Potential of Dental Pulp Stem Cells and Leukocyte- and Platelet-Rich Fibrin for Osteoarthritis

Monaco

Gervois

Beaumont

et al. 2020

Cells

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Osteoarthritis (OA) is a degenerative and inflammatory joint disorder with cartilage loss. Dental pulp stem cells (DPSCs) can undergo chondrogenic differentiation and secrete growth factors associated with tissue repair and immunomodulation. Leukocyte-and platelet-rich fibrin (L-PRF) emerges in regenerative medicine because of its growth factor content and fibrin matrix. This study evaluates the therapeutic application of DPSCs and L-PRF in OA via immunomodulation and cartilage regeneration. Chondrogenic differentiation of DPSCs, with or without L-PRF exudate (ex) and conditioned medium (CM), and of bone marrow-mesenchymal stem cells was compared. These cells showed differential chondrogenesis. L-PRF was unable to increase cartilage-associated components. Immature murine articular chondrocytes (iMACs) were cultured with L-PRF ex, L-PRF CM, or DPSC CM. L-PRF CM had pro-survival and proliferative effects on unstimulated and cytokine-stimulated iMACs. L-PRF CM stimulated the release of IL-6 and PGE2, and increased MMP-13, TIMP-1 and IL-6 mRNA levels in cytokine-stimulated iMACs. DPSC CM increased the survival and proliferation of unstimulated iMACs. In cytokine-stimulated iMACs, DPSC CM increased TIMP-1 gene expression, whereas it inhibited nitrite release in 3D culture. We showed promising effects of DPSCs in an in vitro OA model, as they undergo chondrogenesis in vitro, stimulate the survival of chondrocytes and have immunomodulatory effects.

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“…In subjects suffering from OA there is a reduction in antioxidants [47]. Proinflammatory cytokines (IL-1β, IL-6, and TNF-α), chemokines (MIP-Iα and MIP-2), and NO also play an important function in the pathogenesis of joint damage [48][49][50]. In this regard, in this study, it was found that in rats with OA, treated with carnosine or HA or carnosine+HA, the levels of pro-inflammatory cytokines and chemokines were not significantly reduced.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effect of New Carnosine-Hyaluronic Acid Conjugate on the Inflammation and Cartilage Degradation in the Experimental Model of Osteoarthritis

et al. 2020

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Osteoarthritis (OA) is a disease that currently has no cure. There are numerous studies showing that carnosine and hyaluronic acid (HA) have a positive pharmacological action during joint inflammation. For this reason, the goal of this research was to discover the protective effect of a new carnosine conjugate with hyaluronic acid (FidHycarn) on the inflammatory response and on the cartilage degradation in an in vivo experimental model of OA. This model was induced by a single intra-articular (i.ar.) injection of 25 µL of normal saline with 1 mg of monosodium iodoacetate solution (MIA) in the knee joint of rats. MIA injection caused histological alterations and degradation of the cartilage, as well as behavioral changes. Oral treatment with FidHycarn ameliorated the macroscopic signs, improved thermal hyperalgesia and the weight distribution of the hind paw, and decreased histological and radiographic alterations. The oxidative damage was analyzed by evaluating the levels of nitrotyrosine and inducible nitric oxide synthase (iNOS) that were significantly reduced in FidHycarn rats. Moreover, the levels of pro-inflammatory cytokines and chemokines were also significantly reduced by FidHycarn. Therefore, for the first time, the effectiveness of oral administration of FidHycarn has been demonstrated in an osteoarthritis model. In conclusion, the new FidHycarn could represent an interesting therapeutic strategy to combat osteoarthritis. affects the joints that support most of the weight (such as the knees and feet) and the joints we use the most (e.g., hand joints). In a healthy joint, the cartilage shelters the surface of the bones and supports the bones to move liberally against each other. When a joint develops OA, part of the cartilage tapers and the surface becomes coarser. This means the articulation does not move as easily as it should. When the cartilage becomes worn out or damaged, all the tissues within the articulation become more active than usual as the body attempts to repair the damage. However, the reparation processes do not always operate well, and thus, modifications to the joint structure can occasionally cause or contribute to symptoms such as swelling, pain, and ultimately, disability.One of the leading characteristics of OA is collagen deterioration, as suggested by augmented tissue swelling and the loss of proteoglycans [1]. Both collagen destruction and the loss of proteoglycans unfavorably affect the mechanical properties of cartilage. Chondrocytes respond to tissue injury by increasing collagen and proteoglycan synthesis in an attempt to repair the tissue [2]. If repair fails, the damage will progress to articular cartilage degeneration. It is still not clear exactly what causes osteoarthritis. We do know that it is not simply 'wear and tear' and that the danger of developing OA depends on a number of factors.Furthermore, these degradation processes are thought to be largely elicited through excess production of pro-inflammatory and catabolic mediators. Among them, interleukin-1β (IL-1β) has...

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The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis

Cited by 65 publications

References 27 publications

CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis

CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis

Therapeutic Potential of Dental Pulp Stem Cells and Leukocyte- and Platelet-Rich Fibrin for Osteoarthritis

The Protective Effect of New Carnosine-Hyaluronic Acid Conjugate on the Inflammation and Cartilage Degradation in the Experimental Model of Osteoarthritis

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